Work on the synthesis of 10-thia-folic acid, 10-thia-pteroic acid and of their 2,4-diamino analogs having been completed, we are now engaging in the synthesis of the isomers in which the side chains are attached to the 7-position of the pteridine ring. The interaction of these compounds with dihydrofolic acid reductase and with thymidylic acid synthetase, is to be investigated using C.D. and NMR spectroscopy. The reduction of the various analogs to the 7,8-dihydro- and the tetrahydropteridines will be investigated, with special interest in the separation, the conformation, and the biological activity of the enantiomers. Work on the activity of the various compounds in tissue culture has been initiated in collaboration with Dr. Ming-Yu Chu at Brown University.